Clinical Trial 21341

• Overview

  Study Title:

  A Phase II Study of Cemiplimab plus Ziv-Aflibercept for Subjects with Metastatic Uveal Melanoma

  Summary:

  The goal of this clinical research study is to find out if Cemiplimab plus Ziv-Aflibercept is safe and effective in treating your condition of metastatic (spread to other parts of your body) uveal melanoma. This research study will test the study drugs to see if the combination of Cemiplimab plus Ziv-Aflibercept can make tumors shrink or stop growing.

  Objective:

  1. To evaluate the objective response rate (ORR) utilizing RECIST v.1.1. 2. To evaluate progression free survival (PFS). 3. To evaluate overall survival (OS). 4. To evaluate safety and toxicity.

• Treatments

  Therapies:

  Chemotherapy (NOS); Therapy (NOS)

  Medications:

  Cemiplimab (); REGN2810 (Cemiplimab); Ziv-aflibercept ()

• Inclusion Criteria

  Inclusion Criteria:
  • Provision of signed and dated informed consent form.
  • Male or female, aged >/= 18 years old.
  • Life expectancy of greater than 3 months in the opinion of the investigator.
  • Must be willing and able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines.
  • Patients must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed.
  • Patients must have ECOG performance status of 0-1.
  • Patients must have measurable disease, according to RECIST version 1.1.
  • Patients must have normal organ and marrow function as defined in protocol.
  • Urine protein should be screened by urinalysis for Urine Protein Creatinine Ratio (UPCR). For UPCR > 1, a 24-hour urine protein should be obtained, and the level should be > An echocardiogram should be performed at baseline in all patients. Ejection fraction (EF) from baseline echocardiogram must be within the institutional limits of normal as determined by the reading cardiologist.
  • Patients on full-dose anticoagulants (e.g., warfarin) with PT INR >1.5 are eligible provided that both of the following criteria are met: (a) The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin. (b) The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices).
  • A patient may be treatment naïve. However, prior systemic treatments for metastatic uveal melanoma are allowed. There is no limit on the number of prior regimens for metastatic uveal melanoma. However, no prior therapy with bevacizumab, aflibercept or cemiplimab.
  • Patients must be free of active brain metastasis by contrast-enhanced CT/MRI scans within 4 weeks prior to enrollment. If known to have prior brain metastases, these must have been adequately managed with standard of care radiation therapy, stereotactic radiosurgery or surgery prior to registration on the study.
  • For Women of childbearing potential: use of highly effective contraception for at least 2 or more menstrual cycles prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.
  • For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner For at least 1 month prior to screening and agreement to use such a method during study participation and for at least 180 days after the end of study drugs administration.

• Exclusion Criteria

  Exclusion Criteria:
  • Pregnancy or lactation.
  • Treatment with another investigational drug or other systemic intervention for uveal melanoma within 4 weeks of initiation of study drugs. Patients must not have radiotherapy within the preceding 4 weeks.
  • Patients must have recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Patients must be at least 4 weeks from major surgery and have fully recovered from any effects of surgery and be free of significant detectable infection.
  • Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (i.e., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids. A history of occasional (but not continuous) use of steroid inhalers is allowed. Replacement doses of steroids for patients with adrenal insufficiency are allowed. Patients who discontinue use of these classes of medication for at least 2 weeks prior to enrollment are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study.
  • Exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motorneuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis); other central nervous system autoimmune disease (e.g., poliomyelitis, Multiple sclerosis).
  • Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab/placebo. NOTE: Patients who require brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded. People taking steroids for physiologic replacement (ie, adrenal insufficiency) are NOT excluded.
  • Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
  • Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug related toxicity.
  • Encephalitis, meningitis, or uncontrolled seizures in the year prior to screening/enrollment.
  • History of immune related pneumonitis within the last 5 years.
  • History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved >/= 6 months prior to the enrollment date.
  • Patients with a history of solid organ transplant (patients with prior corneal transplant(s) are not excluded).
  • Patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible.
  • Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed).
  • Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of cemiplimab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  • Patients must not have an active infection requiring current treatment with parenteral antibiotics.
  • Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, serious cardiac arrhythmias, or unstable angina.
  • Other exclusions apply

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